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Cancer Drug Information

  • Updated: 03/28/2014

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FDA Approval for Docetaxel

Brand name(s): Taxotere®

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

Head and Neck Cancer

On October 17, 2006, the FDA approved docetaxel (Taxotere® Injection Concentrate, made by Sanofi-Aventis) for use in combination with cisplatin and fluorouracil for the induction treatment of patients with inoperable, locally advanced squamous cell carcinoma of the head and neck (SCCHN).

The safety and efficacy of docetaxel as induction chemotherapy for patients with SCCHN were evaluated in a multicenter, open-label, randomized trial. In this study, 358 patients with previously untreated inoperable, locally advanced SCCHN, and WHO performance status 0 or 1, received either docetaxel 75 mg/m2 followed by cisplatin 75 mg/m2 on Day 1, followed by 5-fluorouracil 750 mg/m2/day as a continuous infusion on Days 1-5 (TPF), or cisplatin 100 mg/m2 on Day 1, followed by 5-fluorouracil 1000 mg/m2/day as a continuous infusion on Days 1-5 (PF).

These regimens were administered every three weeks for four cycles. Four to seven weeks after chemotherapy, patients whose disease had not progressed received radiotherapy. Radiation was delivered either with a conventional or an accelerated/hyperfractionated regimen. Surgical resection was allowed following chemotherapy, before or after radiotherapy.

The trial’s primary endpoint was progression-free-survival (PFS) and was defined as time from randomization to disease progression or death from any cause, whichever occurred first. Median PFS was significantly longer in the TPF arm (11.4 months) than in the PF arm (8.3 months), (p= 0.0077) [hazard ratio 0.71 (0.56, 0.91)].

Median overall survival was significantly longer in the TPF arm (18.6 months) than in the PF arm (14.2 months), [hazard ratio 0.71 (0.56, 0.90)].

The most frequent adverse events on the TPF arm were

  • neutropenia (93 percent)
  • anemia (89 percent)
  • alopecia (81 percent)
  • stomatitis/esophagitis (55 percent)
  • nausea (47 percent)

Grade 3 or 4 adverse events with a greater than 5 percent frequency in patients on the TPF arm were

  • neutropenia (76 percent)
  • alopecia (11 percent)
  • infection (9 percent)
  • anemia (9 percent)
  • weight loss (7 percent)
  • thrombocytopenia (5 percent)

Approximately 5 percent of the TPF arm patients had febrile neutropenia and 14 percent had neutropenic infection. Compared to patients receiving PF, patients receiving TPF had more alopecia, neutropenia, diarrhea, neurosensory abnormality, neutropenic infection, fluid retention, and altered taste or sense of smell.

For this SCCHN indication, the recommended docetaxel dose is 75 mg/m2 administered as a one-hour intravenous infusion, followed by cisplatin 75 mg/m2 intravenously over one hour on Day 1, followed by fluorouracil 750 mg/m2/day given as a 24-hour intravenous continuous infusion Days 1-5. Treatment is repeated every three weeks for four cycles.

On September 28, 2007, the FDA approved docetaxel for use in combination with cisplatin and fluorouracil (5-FU) for the induction treatment of patients with locally advanced SCCHN.

The safety and efficacy of docetaxel for the above indication were evaluated in a multicenter, open-label, randomized trial. In this study, 501 patients with previously untreated locally advanced SCCHN, and performance status 0 or 1, received either docetaxel 75 mg/m2 followed by cisplatin 100 mg/m2 on day 1, followed by 5-FU 1000 mg/m2/day as a continuous infusion on Days 1-4 (TPF) or cisplatin 100 mg/m2 on Day 1, followed by 5-FU 1000 mg/m2/day as a continuous infusion on Days 1-5 (PF).

These regimens were administered every three weeks for three cycles. All patients in both treatment arms who did not have progressive disease following induction chemotherapy received seven weeks of chemoradiotherapy (CRT). During radiotherapy, carboplatin (AUC 1.5) was administered weekly as a one-hour infusion for a maximum of seven doses. Surgery could be considered at anytime following completion of CRT.

Overall survival was significantly prolonged with the docetaxel-containing regimen compared to the PF regimen (log­rank test, p=0.0058). The median survival was 70.6 months in the TPF group compared to 30.1 months in the PF group (hazard ratio = 0.70, 95 percent confidence interval: 0.54, 0.90).

The most frequent adverse events (>40 percent, any grade) on the TPF arm were neutropenia, anemia, nausea, alopecia, stomatitis, lethargy, vomiting, diarrhea, and anorexia. Neutropenic fever with or without infection occurred in greater than 5 percent of patients on the TPF arm. Grade 3 or 4 adverse events with a greater than 5 percent frequency in patients on the TPF arm were neutropenia, infection, stomatitis, nausea, esophagitis/dysphagia/odynophagia, anorexia, vomiting, and anemia. Neutropenia, alopecia, diarrhea, and anorexia were more frequently seen in the TPF arm.

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Gastric Cancer

On March 22, 2006, the U.S. Food and Drug Administration (FDA) approved docetaxel (Taxotere® Injection Concentrate, made by Sanofi-Aventis) for use in combination with cisplatin and fluorouracil for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease.

This indication is based on the results of a multicenter, open-label, comparative clinical trial of 457 patients with locally advanced or metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for advanced disease. Patients were randomized to one of two arms.

  • TCF (docetaxel 75 mg/m² in combination with cisplatin 75 mg/m² on Day 1 and fluorouracil 750 mg/m²/day by continuous infusion for five days every three weeks), or
  • CF (cisplatin 100 mg/m² on Day 1 and fluorouracil 1000 mg/m²/day by continuous infusion for five days every four weeks). Four hundred and forty five patients were treated (TCF = 221, CF = 224)

Time-to-progression (TTP) was the trial’s primary endpoint and was defined as time from randomization to disease progression or death from any cause within 12 weeks of the last evaluable tumor assessment or within 12 weeks of the first infusion of study drugs for patients with no evaluable tumor assessment after randomization.

The hazard ratio (HR) for TTP was 1.47 (CF/TCF, 95 percent CI: 1.19-1.83) with a significantly longer TTP (p=0.0004) in the TCF arm. The median TTP in the TCF arm was 5.6 months compared to 3.7 months in the CF arm.

Overall survival was significantly longer (p=0.02) in the TCF arm with a HR of 1.29 (95 percent CI: 1.04-1.61). The median survival was 9.2 months in the TCF arm and 8.6 months in the CF arm.

Compared to patients receiving CF, patients receiving TCF had more neutropenia, fever, infection, febrile neutropenia, neutropenic infection, allergic reactions, fluid retention or peripheral edema, neurosensory toxicity, dizziness, alopecia, rash, nail changes, diarrhea, esophagitis/dysphagia/odynophagia, gastrointestinal pain or cramping, and tearing than patients receiving CF.

Eighty-two percent of patients on the TCF arm had grade 3 or 4 neutropenia and 32 percent had febrile neutropenia or neutropenic infection. The most frequent causes for treatment discontinuation were GI toxicities, flu-like symptoms and neurosensory toxicity. Patients receiving CF had more thrombocytopenia, vomiting, anorexia, constipation, and altered hearing.

For gastric carcinoma, the recommended dose of docetaxel is 75 mg/m2 administered as a one-hour infusion, followed by cisplatin 75 mg/m2, as a one-to-three hour infusion (both on Day 1 only), followed by fluorouracil 750 mg/m2 per day given as a 24-hour continuous infusion for five days, starting at the end of cisplatin infusion. Treatment is repeated every three weeks.

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Breast Cancer

On August 18, 2004, the FDA approved docetaxel for injection (Taxotere®, a trademark of Aventis Pharmaceuticals, Inc.) for use in combination with doxorubicin and cyclophosphamide for the adjuvant treatment of women with operable node-positive breast cancer.

Investigators enrolled 1491 women with node positive operable breast cancer in an international, multicenter, randomized trial (TAX316). Patients were stratified according to the number of positive axillary lymph nodes (1-3, 4+) and were randomly allocated to receive adjuvant treatment with either docetaxel 75 mg/m2 administered one-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC arm), or doxorubicin 50 mg/m2 followed by fluorouracil 500 mg/m2 and cyclophosphamide 500 mg/m2 (FAC arm). Both regimens were given every three weeks for six cycles. After the last cycle of chemotherapy, patients with positive estrogen and/or progesterone receptors received tamoxifen 20 mg daily for up to five years.

The primary endpoint, disease free survival (DFS), included local and distant recurrences, contralateral breast cancer and deaths from any cause. At a median follow up of 55 months, results from a second interim analysis showed that the TAC regimen has significantly longer DFS than FAC, with an overall reduction in risk of relapse of 25.7 percent (hazard ratio= 0.74; 2-sided 95% CI= 0.60, 0.92, stratified log rank p = 0.0047). At the time of this interim analysis, based on 219 deaths, overall survival was longer for TAC than FAC (hazard ratio=0.69, 2-sided 95% CI=0.53, 0.90). There will be further analysis at the time survival data mature.

Women receiving TAC had an increase in anemia, grade > 3 neutropenia, stomatitis, amenorrhea, fever in absence of infection, hypersensitivity reactions, peripheral edema, neurosensory and skin events compared to those receiving FAC. The toxicity, while significant, did not cause a large number of patients to withdraw from treatment. As with other anthracycline/cyclophosphamide-containing regimens, long-term serious toxicity for the TAC regimen included leukemia (0.4 percent) and congestive heart failure (1.6 percent).

The approved dose of docetaxel for the adjuvant treatment of operable node-positive breast cancer is 75 mg/m2 administered one-hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every three weeks for six cycles.

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Prostate Cancer

On May 19, 2004, the FDA approved docetaxel for injection (Taxotere®, made by Aventis Pharmaceuticals, Inc.) for use in combination with prednisone for the treatment of metastatic, androgen-independent (hormone-refractory) prostate cancer.

Safety and efficacy were demonstrated in TAX327, a randomized, multicenter global clinical trial designed to evaluate chemotherapy with docetaxel and prednisone in the treatment of men with metastatic, hormone-refractory prostate cancer. One thousand and six patients were randomized to one of three treatment arms:

  • mitoxantrone + prednisone (MTX + P),
  • weekly docetaxel (TXT qw) + prednisone, or
  • docetaxel once every three weeks (TXT q3w) + prednisone

The primary efficacy endpoint was survival. The treatment arm of TXT q3w + prednisone demonstrated a statistically significant survival advantage over MTX+P control (median survival 18.9 vs. 16.5 months, respectively, p = 0.0094). The TXT qw + prednisone arm did not demonstrate an advantage in overall survival over the control arm.

Adverse events included anemia, neutropenia, infection, nausea, vomiting, anorexia, and fatigue. Adverse events occurring more frequently with TXT q3w compared to MTX+P included allergic reactions, fluid retention, sensory neuropathy, alopecia, nail changes, diarrhea, and stomatitis.

The approved dose for this indication is 75 mg/m2 docetaxel given intravenously as a one-hour infusion every 21 days on Day 1 plus 5 mg oral prednisone twice daily for 10 cycles.

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Non-Small Cell Lung Cancer

On December 23, 1999, the FDA approved docetaxel for injection (Taxotere®, made by Aventis Pharmaceuticals, Inc.) for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy.

On November 27, 2002, the FDA approved docetaxel for injection, in combination with cisplatin, for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition.

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This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.